10-76557218-G-T

Position:

• chr10-76557218-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001305581.2(LRMDA):​c.611G>T​(p.Gly204Val) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,748 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: LRMDA NM_001305581.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.57

Genes affected

LRMDA (HGNC:23405): (leucine rich melanocyte differentiation associated) This gene encodes a leucine-rich repeat protein. The encoded protein is thought to play a role in melanocyte differentiation. Mutations in this gene have been associated with autosomal recessive oculocutaneous albinism 7 (OCA7). Alternatively spliced transcript variants have been identified. [provided by RefSeq, Mar 2015]

LRMDA (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRMDA	NM_001305581.2	c.611G>T	p.Gly204Val	missense_variant	7/7	ENST00000611255.5	NP_001292510.1
LRMDA	NM_032024.5	c.527G>T	p.Gly176Val	missense_variant	6/6		NP_114413.1
LRMDA	NR_131178.2	n.965G>T		non_coding_transcript_exon_variant	8/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRMDA	ENST00000611255.5	c.611G>T	p.Gly204Val	missense_variant	7/7	5	NM_001305581.2	ENSP00000480240.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251456 Hom.: 0 AF XY: 0.00000736 AC XY: 1 AN XY: 135898

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461748 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727196

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.45
BayesDel_addAF	Benign	-0.092	T
BayesDel_noAF	Benign	-0.20
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.17	.;T;.
Eigen	Pathogenic	0.84
Eigen_PC	Pathogenic	0.83
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.86	D;D;D
M_CAP	Uncertain	0.11	D
MetaRNN	Uncertain	0.67	D;D;D
MetaSVM	Benign	-0.32	T
PROVEAN	Pathogenic	-5.4	.;D;.
REVEL	Uncertain	0.39
Sift	Uncertain	0.0040	.;D;.
Sift4G	Uncertain	0.0030	D;D;D
Polyphen		1.0	.;D;.
Vest4		0.57
MutPred		0.52		.;Loss of loop (P = 0.0112);.;
MVP		0.90
MPC		0.62
ClinPred		0.99	D
GERP RS		6.0
Varity_R		0.73
gMVP		0.60

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs75852090; hg19: chr10-78316976;